The effect of a new nitro-aspirin on apoptosis of neutrophil granulocytes

Apoptosis of neutrophil granulocytes is a critical event in the
resolution of inflammation. Neutrophils have a short lifespan which can
be modulated by aspirin. In this work we studied the effect of a nitroaspirin
(NCX4040) on apoptosis of inflammatory granulocytes. This
nitro-aspirin has been synthesized in attempt to reduce the side effects
of aspirin in the gastrointestinal tract. Inflammatory granulocytes have
been isolated from polyvinyl sponges implanted under the skin of
Albino Oxford (AO) rats. Inflammatory cells that were isolated 20 hours
later were about 95% neutrophil granulocytes. The cells were cultivated
24h with different concentrations of NCX4040 ranging from 0.01 μM to
10μM. After that period, apoptosis of neutrophils was performed by
using morphological criteria, as well as by flow cytometry (after staining
the cells with propidium iodide). We found that NCX4040 at
concentrations from 0.25 to 10 μM induced the apoptosis of rat
inflammatory granulocytes in a dose-dependent manner. Also, in these
concentrations NCX4040 decreased production of nitric oxide in the
cells culture supernatants. In conclusion, our results suggest that antiinflammatory
properties of NO-aspirins are additionally potentiated by
their proapoptotic effect on granulocytes, which could be a novel
mechanism of their action.